School of Physical and Mathematical Sciences
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Browsing School of Physical and Mathematical Sciences by Author "Ankrah, N.A."
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Item Targeting of Tlck-Coupled Liposome to Simian Virus 40 Transformed Mouse Fibroblasts(University of Ghana, 1984-08) Ankrah, N.A.; Wei R.; Flechtner W.T.; University of Ghana, College of Basic and Applied Sciences, School of Physical and Mathematical Sciences, Department of Chemistry.N-a-tosyl-L-lysyl-chloromethyl ketone (TLCK) has been coupled to ara-C or colchicine encapsulated liposomes via glutaraldehyde treated liposomal phosphatidylethanolamine (Lp-G-TLCK) or sodium metaperiodate oxidized oligosaccharide side chain of liposomal digoxin (Lp-D-TLCK). TLCK has been shown to react with specific histidine residue at the active site of such protein as trypsin and has high binding affinity for simian virus 40 and polyoma virus transformed fibroblasts. A 20-minute exposure of cells to Lp-G-TLCK containing ara-C impaired the growth of tumor cells (SVT2 ) for up to two days, but did not impair the growth of normal cells (Balb/C 3T3). However, at 50-minute exposure, the Lp-G-TLCK containing ara-C impaired the growth of Balb/C 3T3 cells at day one but recovered by the second day. The SVT2 cells, on the other hand, did not recover from the cytotoxic effect of Lp-GTLCK, containing ara-C during the second day. The underivatized liposome (Lp-PE) containing ara-C was cytotoxic to both Balb/C 3T3 and SVT2 cells at 20 or 50 minute exposure periods. The Lp-D containing ara-C, at 20 to 60-minute exposure, slightly impaired the growth of SVT2 and Balb/C 3T3 cells at day one. Such cytotoxic effect was, however, not observed by the second and third days of growth. In contrast, Lp-D-TLCK containing ara-C impaired the growth of SVT^ cells while the growth of Balb/C 3T3 cells was nearly indistinguishable from control cells over a threeday period. Thus TLCK selectively enhanced ara-C encapsulated Lp-D-TLCK SVT2 cell cytotoxicity. Lp-D-TLCK containing colchicine, while impairing the growth of Balb/C 3T3 cells, was particularly cytotoxic to SVT2 cells, indicating that colchicine may be an unsuitable anti-tumor drug for use in a culture system with normal cells in their exponential growth phase. The uptake of Lp—D—TLCK by SVT2 cells was higher than the uptake by Balb/C 3T3 cells. With respect to underivatized liposome (Lp-D) the uptake by Balb/C 3T3 cells was higher than the uptake by SVT2 cells, indicating that TLCK enhanced liposome reaction with SVT2 cells and may retard reaction with the Balb/C 3T3 cells.